Hypertension is the most common of all cardiovascular diseases afflicting about 10-20% adult population. Several classes of drugs may be used in the treatment and management of hypertension such as alpha-adrenoceptor antagonists, ACE inhibitors, angiotensin I chymase inhibitors, renin inhibitors, angiotensin II antagonists, vasopressin V.sub.1 antagonists, endothelin antagonists, endothelin-converting enzyme inhibitors, potassium channel activators, calcium channels antagonists, adenosine A.sub.2 agonists, adenosine A.sub.1 antagonists, neutral endopeptidase inhibitiors, dual-action ACE and neutral endopeptidase inhibitors.
These drugs belong to structurally diverse class of heterocyclics including substituted arylpiperazines. In this context, the 1-[4-Arylpiperazin-1-yl]-3-[2-oxopyrrolidin-1-yl]propanes and 1-[4-Arylpiperazin-1-yl]-3-[2-oxopiperidin-1-yl]propanes of the formula 1 are structurally novel compounds and show significant antihypertensive and antiischemic activities. Thus, these compounds would be useful in the treatment of hypertension and in preventing post-ischemic reperfusion injury (ischemia).
The most commonly used antihypertensive drugs are ACE's inhibitors (captopril and related drugs), Ca.sup.++ channel blocker (nifedipine, verapamil, diltiazen) and peripheral alpha.sub.1 -adrenergic antagonist such as prazosin. As these drugs have one or the other side effects, there has been a continuous search for new and safe antihypertensive agents acting by these mechanism and by other novel mechanism which include mainly endothelin antagonists [Gulati, A. and Srimal, R. C. Drug Dev. Res., 26, 361, 1992; Antihypertensive Drugs. The Year's Drug News, 145-167, 1994]. There are no drugs available to prevent post-ischemic reperfusion injury. However, the existing drugs or chemical agents like Ca.sup.++ channel blockers [Hensch, G. Cardiovascular Res., 26, 14, 1992; Karin Pazyklenk, Robert A. Kloner. Cardiovascular Research, 26, 82, 1992], K.sub.ATP openers [Allen W. Gomoll et al., J. Pharmacol. Exp. Ther., 281, 24, 1997; Arthur A. M. Wilde, Cardiovascular Research, 35, 181, 1997] Na.sup.+ /H.sup.+ exchange inhibitors [Worfgang Scholz et al., Cardiovas. Res., 29, 260, 1995], have been shown to promote myocardial salvage and enhance function recovery in vivo, only when given before or during ischemic episode. However, administration of these agents only during reperfusion does not result in cardioprotective activity (Grover, G. J. et al., Cardiovasc. Drugs Ther., 4, 465, 1990 & Eur. J. Pharmacol., 191, 11, 1990; Mizumura, T. et al., Circulation, 92, 1236, 1995). Besides the use of antiischemic agents in prevention of ischemic/reperfusion injury, there is an unmet medical need for agents to treat post-ischemic reperfusion injury which may simulate the real clinical situation of myocardial infarction.